ABSTRACT: THE UNC-CHAPEL HILL SUPERFUND RESEARCH PROGRAM The interdisciplinary Superfund Research Program at the University of North Carolina at Chapel Hill (UNC-SRP) will address serious public health challenges faced by communities in North Carolina (NC) and across the nation related to inorganic arsenic (iAs). The UNC-SRP prioritizes iAs as the focus contaminant as it is highly relevant to millions in NC and the US exposed to unsafe levels. In NC, contamination is derived from both geogenic sources and industrial activities (e.g. superfund sites and coal ash contamination) polluting thousands of private wells. An estimated ~3 million individuals in NC, representing one third of the state?s population, drink water from private wells, with iAs ranging up to 800 ppb. These populations are largely located in the rural areas of NC with established environmental justice conditions. Moreover, iAs contamination reverberates across the state and is locally and nationally-relevant. Related to public health risk, exposure to iAs has been established to be associated with metabolic dysfunction/diabetes. There is a significant gap in the knowledge of factors that drive iAs-induced diabetes risk. The identification of these factors would facilitate development of novel solutions/interventions to reduce the prevalence of iAs-associated diabetes, as well as other diseases associated with iAs exposure. Our unique scientific theme is ?Identifying novel methods to reduce iAs exposure and elucidating mechanisms underlying iAs-induced metabolic dysfunction with a vision for disease prevention.? We address this with three aims: (1) Discover biological mechanisms and susceptibility factors underlying iAs-associated metabolic dysfunction/diabetes; (2) Develop novel methods and technologies to predict iAs contamination and reduce iAs exposure; (3) Translate the science of the UNC-SRP to key stakeholders in NC and the larger SRP program, and engage vulnerable communities. The UNC-SRP comprises five research projects. Projects 1-3 use highly translational techniques spanning in vitro and in vivo models, and human populations to understand mechanisms of iA-induced diabetes. Projects 4-5 advance the ability to predict iAs contamination in private drinking wells and innovative methods for enhanced removal of iAs. With relevance to the national SRP program, we will work with site managers at the Fairfax St. Wood Treaters Superfund site. Five Cores include the Administrative Core, the Community Engagement Core, Data management and Analysis Core (DMAC), Research Experience and Training Coordination Core (RETCC), and Chemistry and Analysis Core (CAC). These Cores facilitate administration, community engagement with our partners Clean Water for NC and the Winyah Rivers Foundation, data management and analysis, training, and chemical analyses. In sum, the UNC-SRP mission is to develop new solutions for iAs reduction and disease prevention through mechanistic and translational research to ultimately inform regulation and Superfund site cleanup efforts.